CONICET | Buscador de Institutos y Recursos Humanos

Stimuli-responsive materials have an emerging importance in nanotechnology and medicine. Temperature, pH and ionic strength are some of the variables in which materials can respond differently and therefore they are able to modulate their behavior. External stimuli may modify material properties, structure, interactions and dimensions. pH-responsive materials are a subgroup of stimuli-responsive materials in which structural and properties change according to the environmental pH. The presence of acidic and basic groups in this type of biomaterial can influence in terms of swelling and drug delivery.[1] In the drug delivery field, stimuli-responsive materials can be used for the development of the controlled release of bioactives[3]. The pH-responsiveness has a special interest due to the fact that the pH in the human body varies between many target tissues and in some pathological conditions such as periodontal disease[4] and cancer.[5]Today, it is important to develop new drug delivery systems that not only play their role as a carrier, but can also have other functions, such as regenerating tissues. [6]In this sense, silica has gained a lot of interest in the past few years. Silica is a bioactive ceramic material, which can promote bone formation. SiO2 is a documented differentiation promoter and its incorporation to delivery systems has improved osteoblast adhesion, differentiation, proliferation and mineralization.[7]Silanol groups from silica could provide a suitable environment for biomineralization. The supersaturation of Ca++ near a negative surface could trigger the nucleation of hydroxyapatite.[8]Periodontal disease is caused by periodontopathogenic bacteria [9] which triggers an inflammatory response that eventually leads to periodontal tissue destruction. At first, gingivitis takes place, the early stage of periodontal disease, which consists in the inflammation of the gingiva. Later, the chronic stage appears, where not only is present inflammation, it is also observed alveolar bone and periodontal ligament destruction.[10] Clearly, silica can play a key role in bone periodontal regeneration.Additionally, mucoadhesive biopolymers such as chitosan (Chi) and carboxymethylcellulose (CMC) are considered as good candidates for oral local delivery. In one hand, chitosan is a marine polysaccharide composed by glucosamine and N-acetyl-glucosamine. On the other, carboxymethylcellulose is a chemically modified biopolymer, derived from cellulose. Although both biopolymers have different structures and properties they present a suitable mucoadhesive profile for oral local drug delivery. CMC is an anionic polymer with outstanding mucoadhesive properties due to the formation of strong hydrogen bonds with the mucin layer. Chi a cationic biopolymer which can bind to the mucosal epithelium via ionic bonds regards to its amino groups and the sialic acid residues of the mucosa.[11]Periodontal disease can be local treated with antioxidants, antimicrobials and inflammatory drugs. For this study, we selected a South American plant called Larrea divaricata with antioxidant and anti-inflammatory properties.[12] Its aqueous extract has promising applications for gingivoperiodontal therapy of diseases that present marked inflammation and periodontal tissue damage. An interesting feature of plant extracts is that their therapeutic effect can be caused by a single active ingredient, a particular phytochemical group or the synergistic action among various compounds. One of the main compounds present in Larrea divaricata leaves is nor-dihydroguayaretic acid (NDGA). Evidently, the use of antioxidants such as Larrea divaricata could treat the harmful effects of chronic inflammation, improving the signs and symptoms of patients with gingivoperiodontal diseases.We present pH-responsive composites loaded with aqueous Larrea divaricata extract that have a differential mucoadhesive profile throughout periodontal disease. Saliva from patients with gingivitis presents a higher pH than the saliva from patients with periodontitis. Additionally, we studied the extract incorporation in two types of composites by a HPLC method as well as the release profile of the composite of the greater incorporation. We also performed preliminary studies of biomineralization to evaluate the potential application of the composites in alveolar bone regeneration.

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